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Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Advanced glycation endproducts (AGEs), final reaction products of protein with sugars, are known to contribute to various disorders, including diabetes, aspects of aging, and neurodegenerative diseases. Recently, we reported elevated levels of serum AGEs in patients with nonalcoholic steatohepatitis (NASH); further, we found that AGEs induced the generation of reactive oxygen species followed by the proliferation and activation of hepatic stellate cells, a major contributor to liver fibrosis. In this study, to explore the clinical usefulness of AGEs as a biomarker for the attenuation of NASH, we investigated whether the treatment of NASH with dyslipidemia could decrease serum levels of AGEs.

Methods

This study included 43 patients with biopsy-proven NASH with dyslipidemia. Serum glyceraldehyde-derived AGE measurements and clinical laboratory tests were performed periodically during an open-label study of atorvastatin (10 mg daily) for 12 months. Standard weight-loss counseling was continued during the treatment period. Oral glucose tolerance tests and liver density assessment by computerized tomography were performed before and after treatment. Follow-up liver biopsy was performed in 22 patients.

Results

All 43 patients had dyslipidemia. The body mass indexes and serum glucose levels did not change during the treatment. After the treatment, NASH-related metabolic parameters were significantly improved. Serum glyceraldehyde-derived AGE levels were significantly decreased (10.4 ± 3.8 and 2.5 ± 1.1 IU/mL before and after treatment, respectively). The steatosis grade and nonalcoholic fatty liver disease (NAFLD) activity score were significantly improved.

Conclusions

The present data demonstrated that atorvastatin decreased the serum levels of AGEs in NASH patients with dyslipidemia and suggest the usefulness of AGEs as a biomarker for the attenuation of NASH.

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Abbreviations

NASH:

Nonalcoholic steatohepatitis

NAFLD:

Nonalcoholic fatty liver disease

IR:

Insulin resistance

glycer-AGE:

Glyceraldehyde-derived advanced glycation endproducts

AGEs:

Advanced glycation endproducts

RAGE:

Receptor for AGEs

ROS:

Reactive oxygen species

TBARS:

Thiobarbituric acid reactive substances

OGTT:

Oral glucose tolerance test

IGT:

Impaired glucose tolerance

DM:

Diabetes mellitus

HOMA-IR:

Homeostasis model-IR: NAS

NAFLD:

Activity score

IGT:

Impaired glucose tolerance

BMI:

Body mass index

TNF-α:

Tumor necrosis factor-α

FFA:

Free fatty acid

P-III-P:

Procollagen type III propeptide

HMG-CoA:

3-Hydroxy-3-methylglutaryl-coenzyme A

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Authors and Affiliations

  1. Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan

    Yuki Kimura, Hideyuki Hyogo, Tomokazu Ishitobi, Yoshitaka Nabeshima & Kazuaki Chayama

  2. Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan

    Sho-ichi Yamagishi

  3. Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Toyama, Japan

    Masayoshi Takeuchi

  4. Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

    Koji Arihiro

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  1. Yuki Kimura
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  2. Hideyuki Hyogo
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  3. Sho-ichi Yamagishi
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Correspondence to Hideyuki Hyogo.

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Kimura, Y., Hyogo, H., Yamagishi, Si. et al. Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH. J Gastroenterol 45, 750–757 (2010). https://doi.org/10.1007/s00535-010-0203-y

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  • DOI: https://doi.org/10.1007/s00535-010-0203-y

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